Methyl ethyl ketone, condensation with aldehydes

Aldehydes and ketones such as acetaldehyde, ben2aldehyde, acetone, acetophenone, cyclohexanone, cyclopentanone, and methyl ethyl ketone have been condensed with CPD in the presence of alkaline agents to produce colored hilvene derivatives. A typical condensation with a ketone is depicted as follows ... 

Bohlmann (207) reported the reaction of /I -dehydroquinolizidine with methyl vinyl ketone and with propargyl aldehyde forming a partially saturated derivative of julolidine 135 and julolidine (136), respectively. Compound 135 can be prepared also by mercuric acetate dehydrogenation of ketone 137, which is formed by condensation of 1-bromoethylquinolizi-dine with ethyl acetoacetate (Scheme 11). 

Condensation of3,5-Dimethoxybenzaldehyde with Methyl Ethyl Ketone. 1 mole of the aldehyde is mixed with 3 moles of ketone and a 7% NaOH solution. This mixture is heated to 70-80° for 4 hours. The resulting product is recrystallized from petroleum ether to give a 65% yield of white needles. Mp 70-71°. 

Ethylene glycol in the presence of an acid catalyst readily reacts with aldehydes and ketones to form cyclic acetals and ketals (60). 1,3-Dioxolane [646-06-0] is the product of condensing formaldehyde and ethylene glycol. Applications for 1,3-dioxolane are as a solvent replacement for methylene chloride, 1,2-dichloroethane, 1,1,1-trichloroethane, and methyl ethyl ketone as a solvent for polymers as an inhibitor in 1,1,1-trichloroethane as a polymer or matrix interaction product for metal working and electroplating in lithium batteries and in the electronics industry (61). 1,3-Dioxolane can also be used in the formation of polyacetals, both for homopolymerization and as a comonomer with formaldehyde. Cyclic acetals and ketals are used as protecting groups for reaction-sensitive aldehydes and ketones in natural product synthesis and pharmaceuticals (62). 

Some of the chemistry developed by the industry more recently, to produce new monohydric alcohols, is just as interesting as the linalool chemistry. Sandalore, a recent new Givaudan chemical with a persistent, sandalwood odor is made according to the scheme in Figure 15 (9). Alpha-pinene, the starting material, is converted to the epoxide which is catalytically rearranged to campholen-ic aldehyde. Aldol condensation with methyl ethyl ketone followed by hydrogenation yields Sandalore . 

Dimethyl-188 and 2,6-dimethylpyrazine react very similarly to methylpyrazine. Thus, 2,6-dimethylpyrazine can be converted into a monoanion with sodamide in liquid ammonia which can be condensed with aldehydes and ketones,179 acylated with esters,181 and alkylated with alkyl halides181 to give the corresponding 2-methyl-6-substituted pyrazines. Acylation under suitable conditions also yields diacylated derivatives. Thus, when 2,6-dimethylpyrazine, sodamide, and ethyl benzoate are reacted in 1 3 2 molecular proportion, 38% 2,6-diphen-acylpyrazine (35) and 25% 2-methyl-6-phenacylpyrazine (36) is obtained. From the preparative point of view it is better to form the diacyl derivative by the further acylation of the monoacyl derivative rather than by direct diacylation.187... 

A simpler large scale method to obtain pyrantel, morantel (10a,b) and oxantel (11) involves condensation of 23 with an aryl aldehyde in presence of a base. Water is removed by azeotropic distillation or by using a chemical scavenger like methyl/ethyl formate, which reacts with water to push the reaction in the forward direction (Scheme 3). Other methods to prepare pyrantel and its derivatives are also reported [5,6,13-17]. The l-(2-arylvinyl)pyridium salts (18,19), structural congeners of pyrantel/moratel, are prepared by quaternisation of pyridine with the appropriate bromomethylaryl ketones (27) to afford 28. The latter is reduced with sodium boro-hydride to give the carbinol 29, which on dehydration leads to the formation of l-(2-arylvinyl)pyridinium bromides (18,19) [8]. 

Enol silyl ethers react with aldehydes with a catalytic amount of TBAF to give the aldol silyl ethers in good yields. These reactions generally proceed under very mild conditions and within shorter periods of time than conventional strong acidic or basic conditions. The products from4-f-butyl-l-methyl-2-(trimethylsilyloxy) cyclohexene and benzaldehyde show very good axial selectivity and a little anti-syn selectivity (eq 20). The aldol condensation of ketones and aldehydes can be achieved in one pot when ethyl (trimethylsilyl)acetate is used as a silylation agent with TBAF (eq 21). 

When the aromatic aldehyde contained an ortho hydroxyl or amino group, cyclization to the coumarins or quinolines, respectively, occurred. Attempts to condense ethyl 2- and 4-pyridylacetate (either as the free base or as the methiodide) with phenyl methyl ketone or with o-hydroxyphenyl methyl ketone were unsuccessful. However, the methiodide of the 4-isomer yielded a quinoline when treated with o-aminophenyl methyl ketone. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

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